Overview

Ryvu Therapeutics discovers and develops small molecule therapies that address high value emerging targets in oncology.

Our pipeline is built from internally-discovered candidates which make use of diverse therapeutic mechanisms, including programs directed at targets in the areas of transcriptional regulation, synthetic lethality and immuno-oncology.

Ryvu’s most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with potential to treat hematological malignancies and solid tumors, currently in Phase II development for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) in combination with venetoclax.

SEL24 (MEN1703) is a dual PIM/FLT3 kinase inhibitor in clinical development for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).. Additional programs include synthetic lethality candidates directed at WRN and MTAP deletions as well as immuno-oncology programs focused on STING agonists and HPK1.

  • Clinical Projects
  • Immuno-oncology Collaborations
  • Synthetic Lethality

OUR
RESEARCH

RVU120 SEL24
(MEN1703)
IO WRN PRMT5

Clinical Projects

  • RVU120

    CDK8 is a kinase submodule of the mediator complex, involved in both transcriptional activation and repression. CDK8- mediator complex integrates basal transcriptional machinery with the activity of oncogenic transcriptional and epigenetic factors. Targeting CDK8 and...

  • SEL24 (MEN1703)

    SEL24 (MEN1703) is a selective, dual inhibitor of PIM and FLT3 kinases, two enzymes that are strongly implicated in malignant transformation of hematopoietic cells. The compound is a novel small molecule discovered by Ryvu, and...

Synthetic Lethality

One of the challenges in the development of new oncology therapeutics is the limited number of protein targets known to be addressable with small molecules. Synthetic lethality allows the identification of novel protein targets and mechanisms of cancer cell sensitivity that can be used therapeutically.

Compounds active on specific synthetic lethal targets selectively kill tumor cells of a precisely defined model system, characterized by a specific genetic, epigenetic or metabolic characteristic. This is the approach actively investigated at Ryvu that allows the generation of compounds with highly specific and well-characterized activity.

  • MTA-COOPERATIVE PRMT5 INHIBITOR

    Deletion of 9p21 locus is one of the most frequent genetic alterations associated with human cancers. Apart from tumour suppressor CDKN2A, locus 9p21 contains the gene coding methylthioadenosine phosphorylase (MTAP), the only enzyme capable of...

  • WRN INHIBITOR

    Werner Syndrome helicase (WRN) is a member of the RecQ helicase family and plays an important role in controlling DNA repair mechanisms and maintaining integrity of the genome. WRN helicase has been identified to be...

Novel Targets

Beyond publicly disclosed programs, Ryvu is working on candidates that address novel targets in the areas of synthetic lethality, immuno-oncology and immunometabolism to generate new therapeutics with first-in-class or best-in-class potential.

For the candidates, Ryvu is utilizing a proprietary drug discovery approach combining internally developed expertise and new sophisticated tools and technologies to identify small molecule compounds with favorable profiles and activity.

Immuno-Oncology and other R&D Collaborations

In November 2022, Ryvu Therapeutics and BioNTech have entered into a multi-target research collaboration for several small molecule immunotherapy programs. BioNTech and Ryvu will jointly undertake drug discovery and research projects to develop multiple small molecule programs directed at exclusive targets selected by BioNTech, primarily focused on immune modulation within oncology, with potential applications in other disease areas.

In 2013, Ryvu and Merck KGaA initiated a joint research strategy involving intensive work on multiple targets and several chemical series. The collaboration has successfully completed two milestones and has been expanded over time with additional targets.
The aim of the partnership with Merck is the development of new anticancer therapeutics acting on diverse biological targets associated with aberrant metabolic pathways in cancer cells. Dependence on specific metabolic pathways is a feature of various types of cancer, therefore, targeting this vulnerability has many potential applications in a broad range of patient populations.
The collaboration has resulted in scientific achievements, the joint filing of patent applications and data presentations at international scientific conferences.

In 2022 Ryvu and Exelixis signed an exclusive license agreement focused on the development of novel targeted therapies utilizing Ryvu’s STING (STimulator of INterferon Genes) technology. The agreement expands Exelixis’ portfolio of biotherapeutics by combining Ryvu’s proprietary small molecule STING agonists and STING biology know-how with Exelixis’ network of expertise and resources in antibody engineering, antibody-drug conjugate (ADC) technologies, and proven history of developing and commercializing oncology therapeutics.

Publications

American Society of Hematology (ASH) Annual Meeting, December 9 –12, 2023

  • Safety and Efficacy Results from CLI120-001 a Phase 1 Study in RR-AML and HRMDS: Update from Higher Dose Levels

    PDF Download
  • Preclinical and Clinical Evidence for Erythroid-Stimulating Activity of RVU120 CDK8/19 Inhibitor in AML and MDS

    PDF Download
  • Novel Clinically Useful Inhibitor of Mediator Complex, RVU120, Relieves Differentiation Block in MDS/AML

    PDF Download
  • Targeting CDK8/CDK19 to Disrupt Leukemic Stem Cell-like Population in Acute Myeloid Leukemia: Exploring RVU120 As a Promising Frontline Therapy

    PDF Download
  • Mediator Kinase/CDK8 Inhibition as a Strategy to Improve FLT3 Inhibitor Activity in Acute Myeloid Leukemia

    PDF Download

San Antonio Breast Cancer Symposium (SABCS), December 5-9, 2023

  • Synergistic Activity of CDK8/19 Inhibitor RVU120 and MEK Inhibitors in Hormone-Negative Breast Cancer: Implications for Targeted Therapy

    PDF Download

European Society for Medical Oncology (ESMO) Congress 2023, October 20-24, 2023

  • Phase I/II trial of RVU120, a CDK8/CDK19 inhibitor, in patients with relapsed/refractory metastatic or advanced solid tumors

    PDF Download

AACR-NCI-EORTC International Conference (ENA) 2023, October 11-15, 2023

  • Discovery of Novel MTA-cooperative PRMT5 Inhibitors as Targeted Therapeutics for MTAP-deleted Cancers

    PDF Download
  • Comprehensive Platform for Unraveling the Molecular Mechanisms and Vulnerabilities of Colorectal Cancer: A Step Forward in Target Discovery

    PDF Download
  • MEN1703/SEL24, A Potent PIM Inhibitor, Demonstrates Promising Anti-Tumor Activity in Activated B Cell Like DLBCL, Mantle Cell Lymphoma and Marginal Zone Lymphoma Cells

    PDF Download